Binding of free immunoglobulin light chains to VpreB3 inhibits their maturation and secretion in chicken B cells.

Claudine Schiff,Olivier Rosnet,Karine Grivel,Carla Blanco-Betancourt,Kirsten Richter

doi:10.1074/jbc.m312169-a200

Claudine Schiff, Olivier Rosnet + Show 3 more

Open Access

https://doi.org/10.1074/jbc.m312169-a200

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Abstract

The VpreB3 gene product was first characterized as an immunoglobulin (Ig) mu heavy chain-binding protein in mouse precursor B (pre-B) cells. Although its function is unknown, it has been proposed to participate in the assembly and transport of the pre-B cell receptor. We have identified a VpreB3 orthologous gene in chicken that is located close to the immunoglobulin light chain (LC) gene cluster and specifically expressed in the bursa of Fabricius. By overexpressing VpreB3 in the DT40 IgM(+) immature chicken B cell line, we have characterized VpreB3 as an endoplasmic reticulum-resident glycoprotein that binds preferentially to free IgLC. However, binding to IgHC is observed in IgLC-deficient DT40 cells. Interaction of VpreB3 with free IgLC is partly covalent and induces retention of free IgLC in the endoplasmic reticulum, preventing their secretion without affecting IgM surface expression. Our results demonstrate that this evolutionarily conserved molecule may play a role in the regulation of the maturation and secretion of free IgLC in B cells. We discuss possible implications in the regulation of the immune response.

Highlights

The B cell receptor (BCR)1 at the surface of immature and mature B cells and the precursor B (pre-B) cell receptor at the surface of developing B cell precursors control cell fates at different levels
The BCR consists of an antigen-binding subunit made of two covalently associated ␮ or ␦ immunoglobulin (Ig) heavy chains (HC), each covalently bound to an Ig light chain (LC)
Our failure to find sequences homologous to VpreB3 in the nearly fully sequenced genome of the bony fish Fugu rubripes argues for an emergence of an ancestral VpreB3 gene between 300 and 400 million years ago, between the radiation of the ray-finned fishes and the reptiles/birds phyla

Summary

Introduction

The B cell receptor (BCR)1 at the surface of immature and mature B cells and the pre-B cell receptor (pre-BCR) at the surface of developing B cell precursors control cell fates at different levels. The VpreB3 gene product was first characterized as an immunoglobulin (Ig) ␮ heavy chain-binding protein in mouse precursor B (pre-B) cells. Using the chicken DT40 immature B cell line, we have demonstrated that binding of free IgLC to VpreB3 negatively regulates their maturation and secretion.

Results

Conclusion